In the medical industry, there is often a need for a laboratory technician, e.g., a cytologist, to review a cytological specimen for the presence of specified cell types. A typical cytological technique is a “Pap smear” test, which involves scraping cells from a woman's cervix and analyzing the cells in order to detect the presence of abnormal cells, a precursor to the onset of cervical cancer. Cytological techniques are also used to detect abnormal cells and diseases in other parts of the human body. Acquired cytological samples are often placed in solution and subsequently collected and transferred to a glass slide for viewing under magnification. Fixative and staining solutions are typically applied to cells on the glass slide, often called a cell smear, for facilitating examination and for preserving the specimen for archival purposes.
Prepared specimens are examined using a microscope, such as the microscope 100 generally illustrated in FIGS. 1A-B, which typically includes a stage 110 attached to a body or frame 101 and having a top surface 112 that supports a specimen slide 200 carrying a biological specimen 202 (e.g., as shown in FIG. 2). One or more control knobs are provided to allow the user to move the stage 110. As shown in FIGS. 1A-B, the microscope 100 may have a coaxial control knob 120 including a first knob 121 for moving the stage 110 in one direction (e.g., “x” direction) and a second knob 122 coaxial with the first knob 121 for moving the stage 110 in a different direction (e.g., “y” direction). A light source 130, such as a tungsten-halogen light source, is positioned below the stage 110 to illuminate the specimen 202. Objective lenses 140 form a magnified image of the specimen 202, and a cytologist may view the magnified image through an ocular lens 150. Focus adjustments may be made using another coaxial control knob 160 for adjusting the focus, e.g., moving the stage 110 in a “z” direction. A typical control knob 160 includes a first knob 161 that is used for fine focus or fine stage 110 adjustments in the “z” direction, and a second knob 162 that is used for coarse focus adjustments. Further aspects of microscope components are described in U.S. Publication No. 2007/0139638 A1, the contents of which are incorporated herein by reference.
Machine vision devices and automated systems have also been utilized to acquire and analyze images of biological specimens. One known automated system 300 shown in FIG. 3 includes an automated imaging microscope or station 310, a processing server 320 and an automated review station 330.
One known imaging station 310 includes a camera 312 that acquires images of a specimen 202 on a slide 200 supported by a motorized stage 314 and viewed through an imaging microscope 316 or “imaging scope” 316. Image data 318 generated by the camera 312 is provided to the server 320 that includes one or more processors 321-323 (generally referred to as processor 321) and a memory 324 for processing image data 318 and storing processing results, which are provided to the review station 330. In some automated screening systems, the processor 321 delineates between normal and abnormal or suspicious biological material within each specimen 202. That is, the processor 321 uses diagnostic information to determine the most pertinent biological objects and their locations (e.g., x-y coordinates) on the slide 200. In one system, for example, the server 320 processes image data 318 to identify “objects of interest” (OOIs) in the image data 318. OOIs may take the form of individual cells and cell clusters of the specimen 202. One or more OOIs 710 can be organized within a defined boundary or fields of view of Fields of Interest (FOI), which may be defined by various geometries to include different numbers of OOIs 710 and identified based on (x,y) coordinates. One known automated system identifies 22 FOIs. Further aspects of OOIs and FOIs are described in U.S. Pat. Nos. 7,083,106 and 2004/0254738, the contents of which are incorporated herein by reference.
The processor 321 may be configured to rank identified OOIs based on the degree to which certain cells or objects are at risk of having an abnormal condition such as malignancy or pre-malignancy. The processor 321 may evaluate OOIs for their nuclear integrated or average optical density, and rank the OOIs according to optical density values. The OOI/FOI information may be stored for subsequent processing, review or analysis using the review station 330. One known review microscope 336 automatically proceeds to the 22 FOI locations such that the cytologist may review the OOIs in each FOI. In one automated system, the review station 330 includes a mouse-like joystick that is used to navigate the slide 200. For example, one system includes “NEXT” and “PREVIOUS” buttons that are used to navigate the next and previous FOI. During review, the cytologist can electronically mark OOIs having attributes consistent with malignant or pre-malignant cells for further review by a pathologist by pressing a “MARK” button to identify a particular OOI, e.g., by (x,y) coordinates. An “OBJECTIVE” button may be used to change the objective magnification.
In certain other systems, a motorized stage is retrofitted onto a known microscope, e.g., as shown in FIGS. 1A-B, and coaxial control knobs, which are the same as or similar to control knobs 121, 122 shown in FIGS. 1A-B, may be used to position the stage 110. In certain known systems, automated review functions are controlled using a desktop mouse/graphical user interface and a footswitch that is manipulated by a cytologist to advance through different fields of view or fields of interest.
FIG. 4 illustrates another control mechanism 400 for an automated microscope that includes a base 410, a vertical support 420 extending from the base 410, a lateral support 430, and multiple rotary knobs 441a-c attached to one or more supports 420, 430. Two rotary knobs 441a, 441b are used to control movement of the stage in the “x” and “y” directions, and a third rotary knob 441c is used to control the focus by controlling movement of the stage in the “z” direction. Control of other microscope parameters and settings (such as brightness) is accomplished using one or more push buttons 444a-d on the base 410.
While known automated screening systems and components for controlling microscopes have generally been used effectively, they can be improved. A typical review microscope is configured such that a cytologist's body is positioned in a certain manner to have a certain posture for a comfortable seating position while reviewing specimens through the ocular lenses. In this position, it is often the case that the cytologist's arms are extended to provide support and proper posture, which is particularly important during extended review sessions.
Known control mechanisms, however, typically require a cytologist to utilize different control components that are located at different locations. With such system configurations, a cytologist may either fumble around to locate the controls while looking through the ocular lens to review the specimen, or may be required to look away from the ocular lens and the specimen to locate the controls, manipulate the controls to make the required adjustments, then return his or her eyes to the ocular lens to continue reviewing the specimen. For example, in one known system that includes separate stage control and joystick/review control devices, a cytologist have to look away from the specimen, locate separate stage control and joystick-like devices, manipulate the joystick, then return to the ocular lens to continue specimen review.
Further, certain cytologists may not be comfortable with review system controls that are provided by an automated system. In these cases, if a cytologist observes cells that look suspicious and require further review, he or she may remove a slide from the review scope, place the slide on an independent manual microscope, e.g., as shown in FIGS. 1A-B, and review the specimen using the independent microscope that includes coaxial (x,y) stage and focus controls as shown in FIG. 1. A cytologist may avoid using an unfamiliar review controls with this technique, but it is not convenient, requires additional equipment, requires the cytologist to look away from the automated review scope and move to another microscope, and increases the time required to complete specimen review.